In infected cells, virus components must be organized at the right place and time to
ensure assembly of infectious virions. From a different perspective, assembly must be
prevented until all components are available. Hypothetically, this can be achieved by
allosterically controlling assembly. Consistent with this hypothesis, here we show that the structure of hepatitis B virus (HBV) core protein dimer, which can spontaneously
self-assemble, is incompatible with capsid assembly. Systematic differences between
core protein in dimer and capsid conformations demonstrate linkage between the intradimer interface and interdimer contact surface. These structures also provide explanations for the capsid-dimer selectivity of some antibodies and activity of assembly effectors. Solution studies suggest that the assembly-inactive state is more accurately an ensemble of conformations. Simulations show that allostery supports controlled assembly and results in capsids that are resistant to dissociation. We propose that
allostery, as demonstrated in HBV, is common to most self-assembling viruses.